EP0673245B1 - Composition pharmaceutique effervescente contenant de l'ibuprofene et son procede de preparation - Google Patents
Composition pharmaceutique effervescente contenant de l'ibuprofene et son procede de preparation Download PDFInfo
- Publication number
- EP0673245B1 EP0673245B1 EP94902008A EP94902008A EP0673245B1 EP 0673245 B1 EP0673245 B1 EP 0673245B1 EP 94902008 A EP94902008 A EP 94902008A EP 94902008 A EP94902008 A EP 94902008A EP 0673245 B1 EP0673245 B1 EP 0673245B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- parts
- weight
- ibuprofen
- pharmaceutically acceptable
- effervescent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Revoked
Links
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 229960001680 ibuprofen Drugs 0.000 title claims abstract description 54
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 8
- 239000000203 mixture Substances 0.000 claims abstract description 41
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 22
- 239000007938 effervescent tablet Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 239000000843 powder Substances 0.000 claims abstract description 16
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 150000007524 organic acids Chemical class 0.000 claims abstract description 13
- 239000003826 tablet Substances 0.000 claims abstract description 11
- 239000007911 effervescent powder Substances 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 35
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 21
- 239000004337 magnesium citrate Substances 0.000 claims description 16
- 229960005336 magnesium citrate Drugs 0.000 claims description 16
- 235000002538 magnesium citrate Nutrition 0.000 claims description 16
- 229940087168 alpha tocopherol Drugs 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 15
- 229960000984 tocofersolan Drugs 0.000 claims description 15
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical group [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 15
- 239000002076 α-tocopherol Substances 0.000 claims description 15
- 235000004835 α-tocopherol Nutrition 0.000 claims description 15
- 235000006708 antioxidants Nutrition 0.000 claims description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 14
- 239000008101 lactose Substances 0.000 claims description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 239000000470 constituent Substances 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 239000000839 emulsion Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 4
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 4
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 235000003599 food sweetener Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 239000003765 sweetening agent Substances 0.000 claims description 3
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 claims description 2
- RPWFJAMTCNSJKK-UHFFFAOYSA-N Dodecyl gallate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 RPWFJAMTCNSJKK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002211 L-ascorbic acid Substances 0.000 claims description 2
- 235000000069 L-ascorbic acid Nutrition 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 2
- 235000010389 delta-tocopherol Nutrition 0.000 claims description 2
- 239000000555 dodecyl gallate Substances 0.000 claims description 2
- 235000010386 dodecyl gallate Nutrition 0.000 claims description 2
- 229940080643 dodecyl gallate Drugs 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 235000010382 gamma-tocopherol Nutrition 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000000574 octyl gallate Substances 0.000 claims description 2
- 235000010387 octyl gallate Nutrition 0.000 claims description 2
- NRPKURNSADTHLJ-UHFFFAOYSA-N octyl gallate Chemical compound CCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 NRPKURNSADTHLJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000473 propyl gallate Substances 0.000 claims description 2
- 235000010388 propyl gallate Nutrition 0.000 claims description 2
- 229940075579 propyl gallate Drugs 0.000 claims description 2
- 229930003799 tocopherol Natural products 0.000 claims description 2
- 239000011732 tocopherol Substances 0.000 claims description 2
- 235000010384 tocopherol Nutrition 0.000 claims description 2
- 229960001295 tocopherol Drugs 0.000 claims description 2
- 239000002478 γ-tocopherol Substances 0.000 claims description 2
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 claims description 2
- 239000002446 δ-tocopherol Substances 0.000 claims description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 5
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 5
- 239000012024 dehydrating agents Substances 0.000 claims 5
- VAUIYOPXEJWUFG-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)C1(C(=C(C(=O)O1)O)O)C(O)CO Chemical compound C(CCCCCCCCCCCCCCC)C1(C(=C(C(=O)O1)O)O)C(O)CO VAUIYOPXEJWUFG-UHFFFAOYSA-N 0.000 claims 1
- 230000001804 emulsifying effect Effects 0.000 claims 1
- 239000000796 flavoring agent Substances 0.000 claims 1
- 125000001020 α-tocopherol group Chemical group 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract description 12
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 9
- 239000002274 desiccant Substances 0.000 description 8
- 238000005469 granulation Methods 0.000 description 6
- 230000003179 granulation Effects 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
- NTJPVVKEZMOHNU-UHFFFAOYSA-N 6-(oxan-4-yl)-1h-indazole Chemical compound C1COCCC1C1=CC=C(C=NN2)C2=C1 NTJPVVKEZMOHNU-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229960000878 docusate sodium Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 235000019321 monosodium tartrate Nutrition 0.000 description 2
- -1 palmityl DL ascorbic acid Chemical compound 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 229940119126 sodium bitartrate Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- FRLGFEJDRMTGHL-YFKPBYRVSA-N (2s)-6-amino-2-(carboxyamino)hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(O)=O FRLGFEJDRMTGHL-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000861223 Issus Species 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the subject of the present invention is a new effervescent pharmaceutical composition containing, as active ingredient, ibuprofen and its preparation process.
- 2- (4-isobutylphenyl) propionic acid known as ibuprofen is a well-tolerated drug with antipyretic and anti-inflammatory analgesic activities (Merk Index, XI edition, No. 4812).
- composition intended for the preparation of an effervescent powder or tablet comprising ibuprofen or one of its pharmaceutically acceptable salts, an effervescent couple capable of producing carbon dioxide in the presence of water, a surfactant and an insoluble hydrophilic polymer.
- ibuprofen is preferably coated with the insoluble hydrophilic polymer (advantageously constituted by microcrystalline cellulose) and it is indicated that in the absence of such a polymer ibuprofen is deposited on the walls of the container in which the effervescent composition is prepared.
- the object of the present invention is to provide a new composition intended for the preparation of effervescent powders or tablets of ibuprofen with improved stability.
- the present invention relates to a pharmaceutical composition intended for the preparation of powders or effervescent tablets containing an effective amount of ibuprofen or one of its pharmaceutically acceptable salts as active ingredient; a pharmaceutically acceptable effervescent system comprising at least one alkaline carbonate and at least one organic acid, characterized in that it comprises at least one pharmaceutically acceptable antioxidant agent, in an amount sufficient to stabilize ibuprofen.
- the present invention is based on the surprising discovery that the stability of ibuprofen, or its pharmaceutically acceptable salts, in contact with alkali carbonates can be considerably improved by a prior treatment of ibuprofen or its pharmaceutically acceptable salts with an antioxidant agent.
- the term “powders” is intended to denote any mixture of components, granulated or not, intended to be dissolved and / or suspended in water, or else to be ingested directly or by any other suitable means such as for example in admixture with a food product.
- the present invention preferably applies to ibuprofen as well as to its insoluble salts such as in particular the calcium salt, but its principle can also be used for the preparation of powders or tablets incorporating soluble salts ibuprofen.
- An alkaline carbonate capable of being used in the context of the present invention is for example sodium bicarbonate, potassium bicarbonate, carboxylysine, calcium carbonate, sodium carbonate, potassium carbonate, as well as mixtures of these compounds.
- sodium bicarbonate will be used.
- organic acids which can be used within the framework of the present invention are compounds capable of reacting with alkali carbonates to cause a release of carbon dioxide, when they are brought into contact with sufficient water.
- Suitable acids are for example citric acid, fumaric acid, adipic acid, tartaric acid as well as mixtures of these compounds.
- the preferred acid is citric acid.
- alkali carbonate and organic acid use will be made of sufficient amounts of alkali carbonate and organic acid to obtain a pH of less than about 8 in the presence of water, and preferably a pH of between 4 and 5.
- the relative weight proportions of these compounds within the effervescent system vary according to the desired pH after dissolution, which is understandable to those skilled in the art, for example for a pH of about 3 to about 7 the ratio varies from about 20/80 to about 80/20.
- this composition also comprises an effective amount of at least one internal desiccant.
- this composition also comprises a pharmaceutically acceptable diluent.
- This diluent also plays a favorable role in stabilizing ibuprofen and its pharmaceutically acceptable salts.
- the abovementioned antioxidant agent is chosen from alpha-tocopherol, gamma-tocopherol, delta-tocopherol, extracts of natural origin rich in tocopherol, L-ascorbic acid and its sodium or calcium salts, palmityl DL ascorbic acid, propyl gallate, octyl gallate, dodecyl gallate, butyl-hydroxy anisole gallate (BHA) and butyl-hydroxy toluene gallate ( BHT).
- the antioxidant agent will be alpha-tocopherol.
- the internal desiccant is magnesium citrate.
- the internal desiccant has the function of trapping traces of water that may appear in the tablet. It has in fact been observed that when it comes into contact with alkaline carbonates, ibuprofen degrades by generating water molecules which further promote the degradation process.
- the diluent is lactose.
- any other pharmaceutically acceptable diluent could be used, in particular sucrose.
- Magnesium citrate can also be used in this function.
- the subject of the present invention is a pharmaceutical preparation, in the form of an effervescent powder or tablet, characterized in that it contains a composition as defined above optionally combined with at least one additive usual chosen from sweeteners, flavorings, colors and lubricants.
- a sweetener can be a natural sugar like sucrose or sorbitol or a synthetic product like saccharin or aspartame.
- saccharin will be used.
- this pharmaceutical preparation will be in the form of an effervescent tablet containing an amount of effervescent composition as defined above corresponding to 200 mg or 400 mg or 600 mg of ibuprofen per tablet.
- this pharmaceutical preparation will be in the form of a powder containing an amount of effervescent composition as defined above corresponding to 200 mg or 400 mg or 600 mg of ibuprofen per dosage unit.
- the pharmaceutical form obtained at the end of the aforementioned process can be directly used in the form of powder and packaged for example in sachets.
- This pharmaceutical form can also be presented as a tablet after a traditional compression step.
- a solution or an emulsion containing the antioxidant agent will be used.
- alpha-tocopherol which is hydrophobic
- a suitable solvent such as for example water or an organic solvent compatible with ibuprofen, that is to say, do not dissolving only weakly.
- a mixture of sodium docusate and polyvinylpyrrolidone has been found to be particularly preferred.
- the treatment of ibuprofen with the antioxidant agent will preferably be carried out by spraying the emulsion containing the antioxidant using the various technologies conventionally used in the pharmaceutical industry such as for example a planetary mixer, a vacuum granulator mixer. , a fluidized bed or a coulter mixer, or a turbine.
- the components of the effervescent system will be subjected to a prior granulation, together or separately, in an appropriate solvent (water, alcohol, dichloromethane, isopropanol, or their mixture).
- an appropriate solvent water, alcohol, dichloromethane, isopropanol, or their mixture.
- the various ingredients of the pharmaceutical form other than the ibuprofen treated by the antioxidant and the effervescent system will preferably be mixed in the form of powders.
- At least one internal desiccant is added such as magnesium citrate as one of the constituents of the pharmaceutical preparation.
- Step a Treatment of ibuprofen with the antioxidant
- Alpha-tocopherol (42.10 -3 ), sodium docusate (75.10 -3 ) and polyvinylpyrrolidone (375.10 -3 ) are mixed in water to obtain an emulsion.
- the emulsion thus obtained is sprayed on ibuprofen (100) then the product thus obtained is dried under vacuum.
- Step b Granulation
- the various components to be granulated are introduced into a granulating mixer, [Sodium bicarbonate (300) - Citric acid (500)].
- the granulation liquid is then sprayed onto the powder bed.
- the mixture obtained is then dried in a fluidized bed.
- the granules obtained are calibrated by means of a grid.
- the product obtained is in the form of a dry powder which can be used directly for the preparation of tablets.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9214851A FR2698788B1 (fr) | 1992-12-09 | 1992-12-09 | Composition pharmaceutique effervescente contenant de l'ibuprofène et son procédé de préparation. |
| FR9214851 | 1992-12-09 | ||
| PCT/FR1993/001216 WO1994013279A1 (fr) | 1992-12-09 | 1993-12-09 | Composition pharmaceutique effervescente contenant de l'ibuprofene et son procede de preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0673245A1 EP0673245A1 (fr) | 1995-09-27 |
| EP0673245B1 true EP0673245B1 (fr) | 1997-09-24 |
Family
ID=9436398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP94902008A Revoked EP0673245B1 (fr) | 1992-12-09 | 1993-12-09 | Composition pharmaceutique effervescente contenant de l'ibuprofene et son procede de preparation |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US5480652A (ru) |
| EP (1) | EP0673245B1 (ru) |
| JP (1) | JP3579421B2 (ru) |
| KR (1) | KR950702414A (ru) |
| AT (1) | ATE158504T1 (ru) |
| AU (1) | AU679200B2 (ru) |
| CA (1) | CA2150945C (ru) |
| CZ (1) | CZ289304B6 (ru) |
| DE (1) | DE69314186T2 (ru) |
| DK (1) | DK0673245T3 (ru) |
| EE (1) | EE03089B1 (ru) |
| ES (1) | ES2110212T3 (ru) |
| FI (1) | FI111517B (ru) |
| FR (1) | FR2698788B1 (ru) |
| GE (1) | GEP19991686B (ru) |
| GR (1) | GR3025634T3 (ru) |
| HU (1) | HU220632B1 (ru) |
| LV (1) | LV11984B (ru) |
| MD (1) | MD872G2 (ru) |
| NZ (1) | NZ258596A (ru) |
| RU (1) | RU2134577C1 (ru) |
| SK (1) | SK281775B6 (ru) |
| TJ (1) | TJ253B (ru) |
| TW (1) | TW280774B (ru) |
| UA (1) | UA27058C2 (ru) |
| WO (1) | WO1994013279A1 (ru) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19502789A1 (de) * | 1995-01-28 | 1996-08-01 | Dirk Krischenowski | Arzneimittel |
| US5639475A (en) * | 1995-02-03 | 1997-06-17 | Eurand America, Incorporated | Effervescent microcapsules |
| DE19606151C2 (de) * | 1996-02-20 | 1999-05-12 | Losan Pharma Gmbh | Ibuprofen-Brausezubereitung sowie Verfahren zur Herstellung derselben |
| US6225123B1 (en) | 1997-04-30 | 2001-05-01 | Becton Dickinson And Company | Additive preparation and method of use thereof |
| US6534016B1 (en) | 1997-04-30 | 2003-03-18 | Richmond Cohen | Additive preparation and method of use thereof |
| GB9721397D0 (en) * | 1997-10-09 | 1997-12-10 | Verdugt Bv | Anticaking agents |
| NZ333474A (en) | 1998-01-02 | 1999-06-29 | Mcneil Ppc Inc | A chewable tablet containing ibuprofen, fumaric acid and a non hydrocolloid binder e.g. a wax or a fat |
| DE19814256A1 (de) * | 1998-03-31 | 1999-10-07 | Asta Medica Ag | Feste, schnellzerfallende Cetirizin-Formulierungen |
| DE19814257A1 (de) * | 1998-03-31 | 1999-10-07 | Asta Medica Ag | Brauseformulierungen |
| IT1301966B1 (it) | 1998-07-30 | 2000-07-20 | Zambon Spa | Composizioni farmaceutiche ad attivita' analgesica |
| DE19962251A1 (de) * | 1999-12-22 | 2001-09-06 | Hermes Fabrik Pharm Praeparate | Lutschtablette |
| EP1303273A1 (en) | 2000-05-26 | 2003-04-23 | Novo Nordisk A/S | New pharmaceutical composition and the process for its preparation |
| AU2000249111A1 (en) * | 2000-05-30 | 2001-12-11 | Dr. Reddy's Research Foundation | New pharmaceutical composition and the process for its preparation |
| AR029538A1 (es) | 2000-07-06 | 2003-07-02 | Wyeth Corp | Composiciones farmaceuticas de agentes estrogenicos |
| US7488496B2 (en) * | 2002-03-06 | 2009-02-10 | Christer Rosen | Effervescent compositions comprising bisphosphonates and methods related thereto |
| EP2277503B1 (en) | 2002-03-06 | 2014-02-12 | EffRx Pharmaceuticals SA | Effervescent compositions comprising bisphosphonates |
| DE102006029233A1 (de) * | 2006-06-26 | 2007-12-27 | Liedtke, Rainer K., Dr. | Formulierungen zur Verbesserung der Verträglichkeit nichtsteroidaler Antiphlogistika |
| EP1902708A1 (de) | 2006-09-25 | 2008-03-26 | Losan Pharma GmbH | Wirkstoff enthaltende stabilisierte feste Arzneimittelformen und Verfahren zu ihrer Herstellung |
| US8445545B2 (en) * | 2008-05-07 | 2013-05-21 | Nicholas DeSica | Pharmaceutical composition, method of preparation and methods of treating aches/pains |
| US10221218B2 (en) | 2011-05-10 | 2019-03-05 | The Regents Of The University Of California | Adenovirus isolated from titi monkeys |
| US9267112B2 (en) | 2011-05-10 | 2016-02-23 | The Regents Of The University Of California | Adenovirus isolated from Titi Monkeys |
| WO2013116112A1 (en) | 2012-02-01 | 2013-08-08 | Kraft Foods Global Brands Llc | Low calorie drink tablet |
| JP5877778B2 (ja) * | 2012-05-28 | 2016-03-08 | 株式会社ホットアルバム炭酸泉タブレット | 錠剤の製造方法及び錠剤 |
| RU2519099C1 (ru) * | 2012-11-08 | 2014-06-10 | Федеральное государственное бюджетное учреждение науки Ордена Трудового Красного Знамени Институт нефтехимического синтеза им. А.В. Топчиева Российской академии наук (ИНХС РАН) | Фармацевтическая композиция |
| FR3060391A1 (fr) * | 2016-12-20 | 2018-06-22 | Promindus Sarl | Composition pharmaceutique anti douleur |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8528195D0 (en) * | 1985-11-15 | 1985-12-18 | Boots Co Plc | Therapeutic compositions |
| CH677606A5 (ru) * | 1988-07-12 | 1991-06-14 | Aesculapius Pharma Sa | |
| US5032384A (en) * | 1989-01-27 | 1991-07-16 | Block Drug Company, Inc. | Compositions and method for the treatment of disease |
| US5178878A (en) * | 1989-10-02 | 1993-01-12 | Cima Labs, Inc. | Effervescent dosage form with microparticles |
-
1992
- 1992-12-09 FR FR9214851A patent/FR2698788B1/fr not_active Expired - Lifetime
-
1993
- 1993-02-08 US US08/014,530 patent/US5480652A/en not_active Expired - Lifetime
- 1993-12-09 CA CA002150945A patent/CA2150945C/fr not_active Expired - Lifetime
- 1993-12-09 DK DK94902008.5T patent/DK0673245T3/da active
- 1993-12-09 UA UA94129149A patent/UA27058C2/ru unknown
- 1993-12-09 NZ NZ258596A patent/NZ258596A/en not_active IP Right Cessation
- 1993-12-09 TJ TJ96000407A patent/TJ253B/xx unknown
- 1993-12-09 RU RU95114402A patent/RU2134577C1/ru active
- 1993-12-09 AT AT94902008T patent/ATE158504T1/de not_active IP Right Cessation
- 1993-12-09 JP JP51386894A patent/JP3579421B2/ja not_active Expired - Lifetime
- 1993-12-09 SK SK728-95A patent/SK281775B6/sk not_active IP Right Cessation
- 1993-12-09 HU HU9501671A patent/HU220632B1/hu unknown
- 1993-12-09 AU AU56536/94A patent/AU679200B2/en not_active Expired
- 1993-12-09 WO PCT/FR1993/001216 patent/WO1994013279A1/fr not_active Application Discontinuation
- 1993-12-09 CZ CZ19951419A patent/CZ289304B6/cs not_active IP Right Cessation
- 1993-12-09 EP EP94902008A patent/EP0673245B1/fr not_active Revoked
- 1993-12-09 KR KR1019950700227A patent/KR950702414A/ko active Search and Examination
- 1993-12-09 GE GEAP19932632A patent/GEP19991686B/en unknown
- 1993-12-09 DE DE69314186T patent/DE69314186T2/de not_active Revoked
- 1993-12-09 ES ES94902008T patent/ES2110212T3/es not_active Expired - Lifetime
- 1993-12-15 TW TW082110660A patent/TW280774B/zh not_active IP Right Cessation
-
1994
- 1994-11-21 FI FI945452A patent/FI111517B/fi not_active IP Right Cessation
- 1994-11-23 EE EE9400211A patent/EE03089B1/xx unknown
- 1994-12-22 MD MD95-0026A patent/MD872G2/ru active IP Right Grant
-
1995
- 1995-06-06 US US08/471,155 patent/US5567437A/en not_active Expired - Lifetime
-
1997
- 1997-10-28 LV LVP-97-214A patent/LV11984B/lv unknown
- 1997-12-10 GR GR970403286T patent/GR3025634T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0673245B1 (fr) | Composition pharmaceutique effervescente contenant de l'ibuprofene et son procede de preparation | |
| KR950002883B1 (ko) | 발포성 커플의 제조방법 | |
| BE1005691A4 (fr) | Composition pharmaceutique a base de ranitidine et son procede de preparation. | |
| EP0361680B1 (en) | Morphine-containing composition | |
| FR2471786A1 (fr) | Composition pharmaceutique seche a liberation lente contenant un excipient sec et procedes pour preparer cette composition et cet excipient | |
| EP2550957B1 (en) | Effervescent formulations of vildagliptin | |
| US4206209A (en) | Sublingual aspirin tablet | |
| JP3119801B2 (ja) | ビタミン含有組成物の安定化方法 | |
| JP2012144560A (ja) | 新規医薬組成物及びその調製のための方法 | |
| JP3195360B2 (ja) | チアガビン塩酸塩を含有する医薬組成物およびその製法 | |
| EP0693926B1 (fr) | Nouvelle composition pharmaceutique destinee a la preparation d'une poudre stable contenant, a titre d'ingredient actif, une association d'acide acetylsalicylique et de metoclopramide | |
| KR100281521B1 (ko) | 프라바스타틴나트륨이 함유된 약제 조성물 | |
| FR2661610A1 (fr) | Nouvelle forme lyophilisee de la diosmine et sa preparation. | |
| FR2580497A1 (fr) | Compositions pharmaceutiques en comprimes | |
| FR2648710A1 (fr) | Composition pharmaceutique a base de ranitidine et son procede de preparation | |
| FR2507084A1 (fr) | Composition antibiotique pour l'administration de la phosphomycine sous forme de comprimes a dissolution lente | |
| EP0643968A1 (fr) | Forme pharmaceutique moulée pour administration orale à base d'acide acétylsalicylique ou de ses sels et son procédé de fabrication | |
| KR20050121497A (ko) | 이트라코나졸의 경구투여용 조성물 및 그 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19941228 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: LABORATOIRES UPSA |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| 17Q | First examination report despatched |
Effective date: 19970526 |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
| REF | Corresponds to: |
Ref document number: 158504 Country of ref document: AT Date of ref document: 19971015 Kind code of ref document: T |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: BOVARD AG PATENTANWAELTE |
|
| GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 19970930 |
|
| ITF | It: translation for a ep patent filed | ||
| REF | Corresponds to: |
Ref document number: 69314186 Country of ref document: DE Date of ref document: 19971030 |
|
| REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Free format text: AVAILABILITY OF NATIONAL TRANSLATION Effective date: 19971002 |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2110212 Country of ref document: ES Kind code of ref document: T3 |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D Free format text: 76691 |
|
| REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 |
|
| PLBQ | Unpublished change to opponent data |
Free format text: ORIGINAL CODE: EPIDOS OPPO |
|
| PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
| PLBQ | Unpublished change to opponent data |
Free format text: ORIGINAL CODE: EPIDOS OPPO |
|
| PLAB | Opposition data, opponent's data or that of the opponent's representative modified |
Free format text: ORIGINAL CODE: 0009299OPPO |
|
| PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
| PLBF | Reply of patent proprietor to notice(s) of opposition |
Free format text: ORIGINAL CODE: EPIDOS OBSO |
|
| 26 | Opposition filed |
Opponent name: ZAMBON GROUP S.P.A. Effective date: 19980623 |
|
| 26 | Opposition filed |
Opponent name: THE BOOTS COMPANY PLC Effective date: 19980624 Opponent name: ZAMBON GROUP S.P.A. Effective date: 19980623 |
|
| R26 | Opposition filed (corrected) |
Opponent name: ZAMBON GROUP S.P.A. Effective date: 19980623 |
|
| NLR1 | Nl: opposition has been filed with the epo |
Opponent name: THE BOOTS COMPANY PLC Opponent name: ZAMBON GROUP S.P.A. |
|
| PLBF | Reply of patent proprietor to notice(s) of opposition |
Free format text: ORIGINAL CODE: EPIDOS OBSO |
|
| PLBF | Reply of patent proprietor to notice(s) of opposition |
Free format text: ORIGINAL CODE: EPIDOS OBSO |
|
| PLBF | Reply of patent proprietor to notice(s) of opposition |
Free format text: ORIGINAL CODE: EPIDOS OBSO |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: IF02 |
|
| PLBQ | Unpublished change to opponent data |
Free format text: ORIGINAL CODE: EPIDOS OPPO |
|
| PLAB | Opposition data, opponent's data or that of the opponent's representative modified |
Free format text: ORIGINAL CODE: 0009299OPPO |
|
| R26 | Opposition filed (corrected) |
Opponent name: ZAMBON GROUP S.P.A. * 19980624 THE BOOTS COMPANY P Effective date: 19980623 |
|
| PLBO | Opposition rejected |
Free format text: ORIGINAL CODE: EPIDOS REJO |
|
| RDAH | Patent revoked |
Free format text: ORIGINAL CODE: EPIDOS REVO |
|
| NLR1 | Nl: opposition has been filed with the epo |
Opponent name: THE BOOTS COMPANY PLC Opponent name: ZAMBON GROUP S.P.A. |
|
| APAC | Appeal dossier modified |
Free format text: ORIGINAL CODE: EPIDOS NOAPO |
|
| APAC | Appeal dossier modified |
Free format text: ORIGINAL CODE: EPIDOS NOAPO |
|
| APAC | Appeal dossier modified |
Free format text: ORIGINAL CODE: EPIDOS NOAPO |
|
| APAC | Appeal dossier modified |
Free format text: ORIGINAL CODE: EPIDOS NOAPO |
|
| APAC | Appeal dossier modified |
Free format text: ORIGINAL CODE: EPIDOS NOAPO |
|
| APCC | Communication from the board of appeal sent |
Free format text: ORIGINAL CODE: EPIDOS OBAPO |
|
| APCC | Communication from the board of appeal sent |
Free format text: ORIGINAL CODE: EPIDOS OBAPO |
|
| APBQ | Date of receipt of statement of grounds of appeal recorded |
Free format text: ORIGINAL CODE: EPIDOSNNOA3O |
|
| APAA | Appeal reference recorded |
Free format text: ORIGINAL CODE: EPIDOS REFN |
|
| APAH | Appeal reference modified |
Free format text: ORIGINAL CODE: EPIDOSCREFNO |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20051117 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20051118 Year of fee payment: 13 Ref country code: NL Payment date: 20051118 Year of fee payment: 13 Ref country code: MC Payment date: 20051118 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DK Payment date: 20051122 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IE Payment date: 20051124 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GR Payment date: 20051125 Year of fee payment: 13 Ref country code: GB Payment date: 20051125 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: PT Payment date: 20051207 Year of fee payment: 13 Ref country code: DE Payment date: 20051207 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20051209 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20051219 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 20051228 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20060104 Year of fee payment: 13 |
|
| PLAB | Opposition data, opponent's data or that of the opponent's representative modified |
Free format text: ORIGINAL CODE: 0009299OPPO |
|
| R26 | Opposition filed (corrected) |
Opponent name: THE BOOTS COMPANY PLC Effective date: 19980624 Opponent name: ZAMBON GROUP S.P.A. Effective date: 19980623 |
|
| NLR1 | Nl: opposition has been filed with the epo |
Opponent name: THE BOOTS COMPANY PLC Opponent name: ZAMBON GROUP S.P.A. |
|
| APBU | Appeal procedure closed |
Free format text: ORIGINAL CODE: EPIDOSNNOA9O |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20061231 Year of fee payment: 14 |
|
| RDAF | Communication despatched that patent is revoked |
Free format text: ORIGINAL CODE: EPIDOSNREV1 |
|
| RDAG | Patent revoked |
Free format text: ORIGINAL CODE: 0009271 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: PATENT REVOKED |
|
| 27W | Patent revoked |
Effective date: 20061024 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| REG | Reference to a national code |
Ref country code: PT Ref legal event code: MP4A Effective date: 20070423 |
|
| NLR2 | Nl: decision of opposition |
Effective date: 20061024 |
|
| REG | Reference to a national code |
Ref country code: SE Ref legal event code: ECNC |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20061227 Year of fee payment: 14 |